Serum neuron-specific enolase:A promising biomarker of silicosis

BACKGROUND Silicosis is a type of chronic pulmonary fibrosis caused by long-term inhalation of silica dust particles.There has been no ideal biomarker for the diagnosis and differential diagnosis of silicosis until now.Studies have found that elevated neuron-specific enolase(NSE)concentration in the serum of silicosis patients is helpful for diagnosis and severity assessment of the disease.However,the number of cases in these studies was not enough to arouse attention.AIM To investigate the clinical significance of serum NSE in the diagnosis and staging of silicosis.METHODS From January 2017 to June 2019,326 cases of silicosis confirmed in Quanzhou First Hospital Affiliated to Fujian Medical University were included in the silicosis group.A total of 328 healthy individuals or medical patients without silicosis were included in the control group.Serum NSE concentrations of all subjects were determined by electrochemical luminescence.RESULTS There were no significant differences in sex,age,smoking index and complications between the silicosis and control groups.The mean serum NSE concentration was 26.57±20.95 ng/mL in the silicosis group and 12.42±2.68 ng/mL in the control group.The difference between the two groups was significant(U=15187,P=0.000).Among the 326 patients with silicosis,103 had stage I silicosis,and the mean serum NSE concentration was 15.55±6.23 ng/mL.The mean serum NSE concentration was 21.85±12.05 ng/mL in 70 patients with stage II silicosis.The mean serum NSE concentration was 36.14±25.72 ng/mL in 153 patients with stage III silicosis.Kruskal-Wallis H test suggested that the difference in serum NSE concentration in silicosis patients in the three groups was significant(H=130.196,P=0.000).Receiver operating characteristic curve analysis indicated that the area under the curve was 0.858(95%confidence interval:0.828-0.888;P=0.000).When the NSE concentration was 15.82 ng/mL,the Jorden index was the largest,the sensitivity was 72%,and the specificity was 90%.CONCLUSION Serum NSE concentration may be a promising biomarker for the diagnosis and assessment of severity of silicosis.

Neuron-specific enolase expression in a rat model of radiation-induced brain injury following vascular endothelial growth factor-modified neural stem cell transplantation

BACKGROUND： Previous studies have shown that transplantation of vascular endothelial growth factor （VEGF）-modified neural stem cells （NSC） provides better outcomes, compared with neural stem cells, in the treatment of brain damage. OBJECTIVE： To compare the effects of VEGF-modified NSC transplantation and NSC transplantation on radiation-induced brain injury, and to determine neuron-specific enolase （NSE） expression in the brain. DESIGN, TIME, AND SETTING： The randomized, controlled study was performed at the Linbaixin Experimental Center, Second Affiliated Hospital, Sun Yat-sen University, China from November 2007 to October 2008. MATERIALS： VEGF-modified C17.2 NSCs were supplied by Harvard Medical School, USA. Streptavidin-biotin-peroxidase-complex kit （Boster, China） and 5, 6-carboxyfluorescein diacetate succinimidyl ester （Fluka, USA） were used in this study. METHODS： A total of 84 Sprague Dawley rats were randomly assigned to a blank control group （n = 20）, model group （n = 20）, NSC group （n = 20）, and a VEGF-modified NSC group （n = 24）. Rat models of radiation-induced brain injury were established in the model, NSC, and VEGF-modified NSC groups. At 1 week following model induction, 10 pL （5 ×10^4 cells/μL） VEGF-modified NSCs or NSCs were respectively infused into the striatum and cerebral cortex of rats from the VEGF-modified NSC and NSC groups. A total of 10μL saline was injected into rats from the blank control and model groups. MAIN OUTCOME MEASURES： NSE expression in the brain was detected by immunohistochemistry following VEGF-modified NSC transplantation. RESULTS： NSE expression was significantly decreased in the brains of radiation-induced brain injury rats （P 〈 0.05）. The number of NSE-positive neurons significantly increased in the NSC and VEGF-modified NSC groups, compared with the model group （P 〈 0.05）. NSE expression significantly increased in the VEGF-modified NSC group, compared with the NSC group, at 6 weeks following transplantation （P 〈 0.05）. CONCLUSION： VEGF-modified NSC transplantation increased NSE expression in rats with radiation-induced brain injury, and the outcomes were superior to NSC transplantation.

Flunarizine and lamotrigine prophylaxis effects on neuron-specific enolase, S-100, and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

BACKGROUND： Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE： To investigate the neuroprotective effects of flunarizine （FNZ）, lamotrigine （LTG） and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING： This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People＇s Hospital, Guangdong Medical College. MATERIALS： Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ ＋ LTG, and model groups, with 10 rats in each group. METHODS： Rats in the FNZ, LTG, and FNZ ＋ LTG groups received intragastric injections of FNZ （0.5 mg/kg/d）, LTG （10 mg/kg/d）, and FNZ （0.5 mg/kg/d） ＋ LTG （10 mg/kg/d）, respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES： Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS： Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ ＋ LTG groups following ischemia, compared with the model group （P 〈 0.01）. However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ ＋ LTG group, following ischemia （P 〈 0.01）. CONCLUSION： Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.

Use of neuron-specific enolase to predict mild brain injury in motorcycle crash patients with maxillofacial fractures: A pilot study

Purpose: Mild traumatic brain injury (TBI) is common but accurate diagnosis and its clinical consequences have been a problem. Maxillofacial trauma does have an association with TBI. Neuron-specific enolase (NSE) has been developed to evaluate neuronl damage. The objective of this study was to investigate the accuracy of NSE serum levels to detect mild brain injury of patients with sustained maxillofacial fractures during motor vehicle accidents. Methods: Blood samples were drawn from 40 healthy people (control group) and 48 trauma patients who has sustained isolated maxillofacial fractures and mild brain injury in motor vehicle accidents. Brain injuries were graded by Glasgow Coma Scale. In the trauma group, correlations between the NSE serum value and different facial fracture sites were also assessed. Results: The NSE serum level (mean ± SD, ng/ml) in the 48 patients with maxillofacial fractures and mild TBI was 13.12 ± 9.68, significantly higher than that measured in the healthy control group (7.72 ± 1.82, p < 0.001). The mean NSE serum level (ng/ml) in the lower part of the facial skeleton (15.44 with SD 15.34) was higher than that in the upper facial part (12.42 with SD 7.68);and the mean NSE level (ng/ml) in the middle-and lower part (11.97 with SD 5.63) was higher than in the middle part (7.88 with SD 2.64). Conclusion: An increase in NSE serum levels can be observed in patients sustained maxillofacial fractures and mild brain injury.

NEURON-SPECIFIC ENOLASE IN PATIENTS WITH ACUTE ISCHEMIC STROKE AND RELATED DEMENTIA

Neuron-specific enolase (NSE) levels of cerebrospinal fluid (CSF) were measured in 39 patients with ischemic stroke and 15 controls. There was a significant increase of CSF NSE in acute ischemic stroke patients as compared with the controls. The altered CSF NSE levels correlated well with the infarct size in CT scan. The CSF NSE levels were higher in 6-multiinfarct dementia (MID) patients who were diagnosed after 6-month follow-up than those in 22 non-MID patients of this series. Our research supports the view that CSF NSE can be a useful biochemical marker for brain ischemia. The importance of CSF NSE in the study of dementia related to ischemic stroke is worth further studies.

Magnetic resonance imaging focused on the ferritin heavy chain 1 reporter gene detects neuronal differentiation in stem cells

The neuronal differentiation of mesenchymal stem cells offers a new strategy for the treatment of neurological disorders.Thus,there is a need to identify a noninvasive and sensitive in vivo imaging approach for real-time monitoring of transplanted stem cells.Our previous study confirmed that magnetic resonance imaging,with a focus on the ferritin heavy chain 1 reporter gene,could track the proliferation and differentiation of bone marrow mesenchymal stem cells that had been transduced with lentivirus carrying the ferritin heavy chain 1 reporter gene.However,we could not determine whether or when bone marrow mesenchymal stem cells had undergone neuronal differentiation based on changes in the magnetic resonance imaging signal.To solve this problem,we identified a neuron-specific enolase that can be differentially expressed before and after neuronal differentiation in stem cells.In this study,we successfully constructed a lentivirus carrying the neuron-specific enolase promoter and expressing the ferritin heavy chain 1 reporter gene;we used this lentivirus to transduce bone marrow mesenchymal stem cells.Cellular and animal studies showed that the neuron-specific enolase promoter effectively drove the expression of ferritin heavy chain 1 after neuronal differentiation of bone marrow mesenchymal stem cells;this led to intracellular accumulation of iron and corresponding changes in the magnetic resonance imaging signal.In summary,we established an innovative magnetic resonance imaging approach focused on the induction of reporter gene expression by a neuron-specific promoter.This imaging method can be used to noninvasively and sensitively detect neuronal differentiation in stem cells,which may be useful in stem cell-based therapies.

Research on the Correlation between NSE Level and Activities of Daily Living in Parkinson’s Disease

Objective: To establish a prediction model of activities of daily living (ADL) as an auxiliary evaluation scheme of hospitalized Parkinson’s disease patients. Methods: The hospitalization data of Parkinson’s disease in patients in the Department of Neurology, Affiliated Brain Hospital of Guangzhou Medical University were collected. Firstly the NSE values and each BI item were analyzed by Pearson correlation analysis. Secondly, The NSE, Age, Body weight and Education level related to the total score of Barthel index were obtained by correlation analysis. At last, a multiple linear regression model was established with NSE, Age, Body weight and Education level as independent variables and BI as dependent variables. Results: A total of 95 patients with PD were enrolled in this study, including 53 males (55.8%) and 42 females (44.2%). The effects of the four independent variables incorporated in the model on the total score of Barthel index were statistically significant, as well as the regression model (F = 9.531, P Conclusion: The prediction model established in this research can effectively predict the activities of daily living of Parkinson’s patients and can be used as an auxiliary evaluation scheme of the hospitalized PD patients.

Choice of serum tumor markers in patients with small cell lung cancer:progastrin-releasing peptide,neuron-specific enolase,and carcinoembryonic antigen

Lung cancer is a leading cause of cancer-related deaths worldwide.It mainly consists of 2 histological types:small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC,including squamous cell carcinoma and adenocarcinoma).The present study aimed to assess the role of serum progastrin-releasing peptide(ProGRP),neuron-specific enolase(NSE),and carcinoembryonic antigen(CEA)and their combinations in the histological diagnosis of lung cancer(specially SCLC),which is of great importance for the initiation of treatment and prognostic implications.Serum ProGRP,NSE,and CEA were determined by the electrochemiluminescence immunoassay(ECLIA)in 66 patients with SCLC,73 with adenocarcinoma,44 with squamous cell carcinoma,45 with non-malignant pulmonary diseases,and 50 healthy controls.Receiver operating characteristic curves were constructed to compare the predictive ability of each biochemical marker and their combined detection models to discriminate among the patients with lung cancers of different histological groups,benign pulmonary diseases and healthy individuals.In the ECLIA detection system,ProGRP showed the sensitivity and specificity for SCLC diagnosis were 71.2%and 91.1%to 93.2%,respectively.Among the markers,the largest area under the ROCs was for ProGRP in discriminating SCLC from benign pulmonary diseases,squamous cell carcinoma and adenocarcinoma(0.815,0.859,and 0.835,respectively),which indicated that ProGRP was the most efficient marker for identifying SCLC.Besides,ProGRP and NSE exhibited almost equivalent diagnostic performance in discriminating SCLC from benign diseases.As for squamous cell carcinoma,we recommended proGRP,while for adenocarcinoma,the combination of proGRP and CEA was preferred.Remarkably,when ProGRP≤66pg/mL,CEA was of great value in diagnosing SCLC and adenocarcinoma.If CEA≤5ng/mL,the patient was at higher risk for SCLC,whereas the patient was more likely to be diagnosed with adenocarcinoma.Our study provided promising information about the diagnostic values of serum ProGRP,NSE,CEA in distinguishing SCLC from benign pulmonary diseases and NSCLC,which was of crucial clinical significance in the early diagnosis and therapy of SCLC.

蚓激酶对急性脑梗死患者血清神经元特异性烯醇化酶的影响

目的:探讨蚓激酶对急性脑梗死患者血液中神经元特异性烯醇化酶的影响及对脑的保护作用。方法:利用酶联免疫吸附法检测60例脑梗死患者蚓激酶治疗过程中血清中的神经元特异性烯醇化酶(neuron-specific enolase,NSE)浓度,记录神经功能NIHSS评分,评定临床疗效,并与对照组进行比较。结果:治疗组第三和第七天血液中NSE浓度明显下降,低于对照组,第十四、二十八天神经功能评分也明显少于对照组(P<0.05)。结论:蚓激酶对脑神经元有保护作用,能有效改善急性脑梗死患者的神经功能缺损。

Platelet-rich fibrin-induced bone marrow mesenchymal stem cell differentiation into osteoblast-like cells and neural cells

Bone marrow mesenchymal stem cells were allowed to develop for 14 days in a platelet-rich fibrin environment.Results demonstrated that platelet-rich fibrin significantly promoted bone marrow mesenchymal stem cell proliferation.In addition,there was a dose-dependent increase in Runt-related transcription factor-2 and bone morphogenetic protein-2 mRNA expression,as well as neuron-specific enolase and glial acidic protein.Results showed that platelet-rich fibrin promoted bone marrow mesenchymal stem cell proliferation and differentiation of osteoblast-like cells and neural cells in a dose-dependent manner.

丙泊酚与异氟烷麻醉对急性颅脑外伤患者脑保护作用的比较

目的：比较丙泊酚与异氟烷麻醉对急性颅脑外伤（aTBI）患者的脑保护作用。方法：100例行急诊手术的a TBI患者按随机数字表法分为丙泊酚组和异氟烷组,各50例。两组患者术中分别应用丙泊酚[4-8 mg/（kg·h）]＋芬太尼＋维库溴铵和异氟烷（吸入浓度0.8%-1.2%）＋芬太尼＋维库溴铵作为麻醉维持药物。比较两组患者术前、手术进行2 h和手术结束时的血清S100B蛋白和神经元特异性雌烯醇化酶（NSE）水平;并比较两组患者术后6个月的简易精神状态检查量表（MMSE）评分。结果：两组患者手术进行2 h和手术结束时的血清S100B蛋白和NSE水平均较术前显著升高（q=3.536-4.336,P〈0.05）,且在手术结束时丙泊酚组患者的血清S100B蛋白和NSE水平显著低于异氟烷组（t=3.622、3.845,P〈0.05）,差异均有统计学意义。两组患者术后6个月的MMSE评分比较,差异无统计学意义（t=0.614,P〉0.05）。结论：针对a TBI患者的手术治疗在消除创伤病灶的同时可造成一定的脑组织损害;与应用异氟烷作为麻醉维持药物相比,术中应用丙泊酚作为麻醉维持药物可降低此类脑组织损害程度,发挥更显著的脑保护作用,但对于患者术后神经功能的恢复无增效作用。

Ginkgolide B promotes the proliferation and differentiation of neural stem cells following cerebral ischemia/reperfusion injury,both in vivo and in vitro

Neural stem cells have great potential for the development of novel therapies for nervous system diseases.However,the proliferation of endogenous neural stem cells following brain ischemia is insufficient for central nervous system self-repair.Ginkgolide B has a robust neuroprotective effect.In this study,we investigated the cell and molecular mechanisms underlying the neuroprotective effect of ginkgolide B on focal cerebral ischemia/reperfusion injury in vitro and in vivo.Neural stem cells were treated with 20,40 and 60 mg/L ginkgolide B in vitro.Immunofluorescence staining was used to assess cellular expression of neuron-specific enolase,glial fibrillary acid protein and suppressor of cytokine signaling 2.After treatment with 40 and 60 mg/L ginkgolide B,cells were large,with long processes.Moreover,the proportions of neuron-specific enolase-,glial fibrillary acid protein-and suppressor of cytokine signaling 2-positive cells increased.A rat model of cerebral ischemia/reperfusion injury was established by middle cerebral artery occlusion.Six hours after ischemia,ginkgolide B（20 mg/kg） was intraperitoneally injected,once a day.Zea Longa＇s method was used to assess neurological function.Immunohistochemistry was performed to evaluate the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells.Real-time quantitative polymerase chain reaction was used to measure m RNA expression of brain-derived neurotrophic factor and epidermal growth factor.Western blot assay was used to analyze the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2.Ginkgolide B decreased the neurological deficit score,increased the proportion of nestin-,neuron-specific enolase-and glial fibrillary acid protein-positive cells,increased the m RNA expression of brain-derived neurotrophic factor and epidermal growth factor,and increased the expression levels of brain-derived neurotrophic factor and suppressor of cytokine signaling 2 in the ischemic penumbra.Together,the in vivo and in vitro findings suggest that ginkgolide B improves neurological function by promoting the proliferation and differentiation of neural stem cells in rats with cerebral ischemia/reperfusion injury.

Intervention of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma

Objective:To study the intervention effect of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma (ASDH).Methods: 160 SD rats were randomly divided into four groups, and the ASDH model rats were made by stereotactic autoblood injection, and sham operation group received craniotomy without blood injection. Sham operation group and model group were normally bred after model establishment, and 6 h after model establishment, the treatment group received intragastric administration of Peiyuan Huayu Decoction, and control group received intragastric administration of Piracetam Tablets, 1 time a day. On the 1d, 3d, 5d and 7d after model establishment, the general conditions of rats (activity, food intake and mental state) were observed, blood was collected via auricula dextra, ELISA method was used to determine peripheral plasma NSE and S100β protein contents, routine HE staining was conducted after perfusion fixation, the neurons in blood injection side of brain tissue were counted, and the neuron damage was observed.Results: 26 rats were dead in the experiment. The general conditions of sham operation group were significantly better than those of other groups, treatment group was significantly better than model group and control group on the 5d group (P<0.05), and there was no significant difference on the 1d, 3d and 7d (P>0.05);neuron count of sham operation group was basically stable, treatment group was not different from model group and control group on the 1d (P>0.05), treatment group was better than model group (P<0.05), and not different from control group (P>0.05) on the 3d, and treatment group was better than model group and control group on the 5d and 7d (P<0.05);peripheral plasma S100β protein and NSE contents of sham operation group were at lower levels, treatment group was not significantly different from model group and control group on the 1d (P>0.05), S100β protein and NSE contents decreased significantly on the 3d, and treatment group was significantly different from model group and control group (P<0.05), S100β protein and NSE contents increased on the 5d and 7d, the increase in treatment group was slower than that in model group and control group, and there was significant difference (P<0.05).Conclusion:Peiyuan Huayu Decoction has obvious protective effect on the neurons in ASDH model rats, and this effect may be based on the inhibition of secondary neuron damage.

Neuronal-like differentiation of bone marrow-derived mesenchymal stem cells induced by striatal extracts from a rat model of Parkinson's disease

A rat model of Parkinson＇s disease was established by 6-hydroxydopamine injection into the medial forebrain bundle. Bone marrow-derived mesenchymal stem cells （BMSCs） were isolated from the femur and tibia, and were co-cultured with 10% and 60% lesioned or intact striatal extracts. The results showed that when exposed to lesioned striatal extracts, BMSCs developed bipolar or multi-polar morphologies, and there was an increase in the percentage of cells that expressed glial fibrillary acidic protein （GFAP）, nestin and neuron-specific enolase （NSE）. Moreover, the percentage of NSE-positive cells increased with increasing concentrations of lesioned striatal extracts. However, intact striatal extracts only increased the percentage of GFAP-positive cells. The findings suggest that striatal extracts from Parkinson＇s disease rats induce BMSCs to differentiate into neuronal-like cells in vitro.

Significance of combined detection of LunX mRNA and tumor markers in diagnosis of lung carcinoma

Objective：To evaluate the significance of combined detection of LunX mRNA,carcinoembryonic antigen （CEA）,neuron-specific enolase （NSE）,and cytokeratin 21-1 fragment （CYFRA21-1） in clinical diagnosis of lung carcinoma.Methods：Based on the quantitative RT-PCR and chemiluminescence immunoassay,the expression levels of LunX mRNA,CEA,NSE,and CYFRA21-1 in 113 patients with lung carcinoma （case group） and 30 healthy participants （control group） were detected.Meantime,the sensitivity,specificity,and accuracy of the combination detection were also explored.Results：The positive rates of LunX mRNA in peripheral blood and CEA,NSE,and CYFRA21-1 in serum were significandy higher in case group than those in control group （x2=17.295,16.825,19.148,and 17.450; P＜0.05）.There was no statistical significance when positive rate of LunX mRNA was evaluated among different pathological types （x2=0.047,P＞0.05）.The positive rate of LunX mRNA in stage Ⅰ ＋ Ⅱ,Ⅲ,and Ⅳ had a significandy increasing tendency （x2=10.565,32.462,P＜0.05）.The positive rate of CYFRA21-1 was highest in squamous carcinoma （78.5％）,the positive rate of NSE was highest in small cell carcinoma （86.7％）,and the positive rate of CEA wag highest in lung adenocarcinoma （80.4％）.The sensitivity and accuracy of the combination detection were 91.1％ and 88.1％,respectively.Conclusions：The combined detection of LunX mRNA and tumor markers （TMs） including CEA,NSE,and CYFRA21-1 in peripheral blood is helpful to increase the diagnostic accuracy of lmg cancer.Also,it can inform the pathological typing of lung carcinoma.

Two outward potassium current types are expressed during the neural differentiation of neural stem cells

The electrophysiological properties of potassium ion channels are regarded as a basic index for determining the functional differentiation of neural stem cells. In this study, neural stem cells from the hippocampus of newborn rats were induced to differentiate with neurotrophic growth factor, and the electrophysiological properties of the voltage-gated potassium ion channels were observed. Immunofluorescence staining showed that the rapidly proliferating neural stem cells formed spheres in vitro that expressed high levels of nestin. The differentiated neurons were shown to express neuron-specific enolase. Flow cytometric analysis revealed that the neural stem cells were actively dividing and the percentage of cells in the S ＋ G2/M phase was high. However, the ratio of cells in the S ＋ G2/M phase decreased obviously as differentiation proceeded. Whole-cell patch-clamp re- cordings revealed apparent changes in potassium ion currents as the neurons differentiated. The potassium ion currents consisted of one transient outward potassium ion current and one delayed rectifier potassium ion current, which were blocked by 4-aminopyridine and tetraethylammonium, respectively. The experimental findings indicate that neural stem cells from newborn rat hippo- campus could be cultured and induced to differentiate into functional neurons under defined condi- tions in vitro. The differentiated neurons expressed two types of outward potassium ion cur＇ents similar to those of mature neurons in vivo.

Optimal therapeutic dose and time window of picroside II in cerebral ischemic injury

A preliminary study from our research group showed that picroside II inhibited neuronal apop- tosis in ischemic penumbra, reduced ischemic volume, and improved neurobehavioral function in rats with cerebral ischemia. The aim of the present study was to validate the neuroprotective effects of picroside II and optimize its therapeutic time window and dose in a rat model of cerebral ischemia. We found that picroside Ⅱ inhibited cell apoptosis and reduced the expression of neuron-specific enolase, a marker of neuronal damage, in rats after cerebral ischemic injury. The optimal treatment time after ischemic injury and dose were determined, respectively, as follows： （1） 2.0 hours and 10 mg/kg according to the results of toluidine blue staining; （2） 1.5 hours and 10 mg/kg according to early apoptotic ratio by flow cytometry; （3） 2.0 hours and 10 mg/kg according to immunohistochemical and western blot analysis; and （4） 1.5 hours and 10 mg/kg according to reverse transcription polymerase chain reaction. The present findings suggest that an intraperitoneal injection of 10 mg/kg picroside II 1.5-2.0 hours after cerebral ischemic injury in rats is the optimal dose and time for therapeutic benefit.

Status epilepticus increases mature granule cells in the molecular layer of the dentate gyrus in rats

Enhanced neurogenesis in the dentate gyrus of the hippocampus following seizure activity, especially status epilepticus, is associated with ectopic residence and aberrant integration of newborn granule cells. Hilar ectopic granule cells may be detrimental to the stability of dentate circuitry by means of their electrophysiological properties and synaptic connectivity. We hypothesized that status epilepticus also increases ectopic granule cells in the molecular layer. Status epilepticus was induced in male Sprague-Dawley rats by intraperitoneal injection of pilocarpine. Immunostaining showed that many doublecortin-positive cells were present in the molecular layer and the hilus 7 days after the induction of status epilepticus. At least 10 weeks after status epilepticus, the estimated number of cells positive for both prospero homeobox protein 1 and neuron-specific nuclear protein in the hilus was significantly increased. A similar trend was also found in the molecular layer. These findings indicate that status epilepticus can increase the numbers of mature and ectopic newborn granule cells in the molecular layer.

Changes of hs-CRP, S100B and NSE levels in serum and cerebrospinal fluid of children with epilepsy and their correlation with the nerve cell apoptosis

Objective:To study the changes of hs-CRP, S100B and NSE levels in serum and cerebrospinal fluid of children with epilepsy and their correlation with the nerve cell apoptosis.Methods:The children who were diagnosed with epilepsy in this hospital between March 2015 and February 2017 were selected as epilepsy group, and the children who underwent operation due to hernia during the same period were selected as control group. The cerebrospinal fluid was collected to determine the contents of hs-CRP, S100B and NSE, and the serum was collected to detect the contents of hs-CRP, S100B, NSE, apoptosis molecules and Sirtuins family molecules.Results: hs-CRP, S100B and NSE levels in serum and cerebrospinal fluid of epilepsy group were significantly higher than those of control group, Bim, Bax, Caspase-3, Caspase-4 and Caspase-9 levels in cerebrospinal fluid were significantly higher than those of control group, and XIAP, Bcl-2, SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7 levels in cerebrospinal fluid were significantly lower than those of control group;hs-CRP, S100B and NSE levels in serum and cerebrospinal fluid of children with epilepsy were positively correlated with Bim, Bax, Caspase-3, Caspase-4 and Caspase-9 levels in cerebrospinal fluid, and negatively correlated with XIAP, Bcl-2, SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6 and SIRT7 levels in cerebrospinal fluid.Conclusion: The abnormally elevated hs-CRP, S100B and NSE in serum and cerebrospinal fluid of children with epilepsy are closely related to the excessive apoptosis of nerve cells.

Effects of Scutellaria baicalensis on neurogenesis in the hippocampal dentate gyrus and on spatial memory of adult rats

We investigated the effects of ethanol extracted Scutellaria baicalensis（EESB） on spatial memory function and neurogenesis in the hippocampal dentate gyrus.Adult Sprague-Dawley rats were orally administered 50,100,or 200 mg/kg of EESB for 6 successive days.The radial-arm maze test showed that 200 mg/kg of EESB improved the spatial memory of adult rats.Confocal microscopy results showed that 100 mg/kg of EESB increased the number of bromodeoxyuridine（BrdU）-and neuron-specific nuclear protein-positive cells in the granular cell layer,and that 100 and 200 mg/kg of EESB increased the number of BrdU-/neuron-specific nuclear protein-positive cells in the sub-granular zone.200 mg/kg of EESB increased the number of BrdU-/glial fibrillary acid protein-positive cells in the subgranular zone.These findings indicate that EESB can effectively promote neurogenesis in the hippocampal dentate gyrus and improve spatial memory function.